Dataset Information

The GOAT-ghrelin system is not essential for hypoglycemia prevention during prolonged calorie restriction.

ABSTRACT:

Objective

Ghrelin acylation by ghrelin O-acyltransferase (GOAT) has recently been reported to be essential for the prevention of hypoglycemia during prolonged negative energy balance. Using a unique set of four different genetic loss-of-function models for the GOAT/ghrelin/growth hormone secretagogue receptor (GHSR) system, we thoroughly tested the hypothesis that lack-of-ghrelin activation or signaling would lead to hypoglycemia during caloric deprivation.

Methodology

Male and female knockout (KO) mice for GOAT, ghrelin, GHSR, or both ghrelin and GHSR (dKO) were subjected to prolonged calorie restriction (40% of ad libitum chow intake). Body weight, fat mass, and glucose levels were recorded daily and compared to wildtype (WT) controls. Forty-eight hour blood glucose profiles were generated for each individual mouse when 2% or less body fat mass was reached. Blood samples were obtained for analysis of circulating levels of acyl- and desacyl-ghrelin, IGF-1, and insulin.

Principal findings

Chronic calorie restriction progressively decreased body weight and body fat mass in all mice regardless of genotype. When fat mass was depleted to 2% or less of body weight for 2 consecutive days, random hypoglycemic events occurred in some mice across all genotypes. There was no increase in the incidence of hypoglycemia in any of the four loss-of-function models for ghrelin signaling including GOAT KO mice. Furthermore, no differences in insulin or IGF-1 levels were observed between genotypes.

Conclusion

The endogenous GOAT-ghrelin-GHSR system is not essential for the maintenance of euglycemia during prolonged calorie restriction.

SUBMITTER: Yi CX

PROVIDER: S-EPMC3283719 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The GOAT-ghrelin system is not essential for hypoglycemia prevention during prolonged calorie restriction.

Yi Chun-Xia CX Heppner Kristy M KM Kirchner Henriette H Tong Jenny J Bielohuby Maximillian M Gaylinn Bruce D BD Müller Timo D TD Bartley Erin E Davis Harold W HW Zhao Yongmei Y Joseph Anupama A Kruthaupt Traci T Ottaway Nickki N Kabra Dhiraj D Habegger Kirk M KM Benoit Stephen C SC Bidlingmaier Martin M Thorner Michael O MO Perez-Tilve Diego D Tschöp Matthias H MH Pfluger Paul T PT

PloS one 20120221 2

<h4>Objective</h4>Ghrelin acylation by ghrelin O-acyltransferase (GOAT) has recently been reported to be essential for the prevention of hypoglycemia during prolonged negative energy balance. Using a unique set of four different genetic loss-of-function models for the GOAT/ghrelin/growth hormone secretagogue receptor (GHSR) system, we thoroughly tested the hypothesis that lack-of-ghrelin activation or signaling would lead to hypoglycemia during caloric deprivation.<h4>Methodology</h4>Male and fe ...[more]

PMID: 22363801

Similar Datasets

Project description:Ghrelin is a gut hormone that signals to the hypothalamus to stimulate growth hormone release, increase food intake and promote fat deposition. The ghrelin receptor, also known as growth hormone secretagogue receptor (GHS-R), is highly expressed in the brain, with the highest expression in agouti-related peptide (AgRP) neurones in the hypothalamus. Compelling evidence indicates that ghrelin serves as a survival hormone with respect to maintaining blood glucose and body weight during nutritional deficiencies. Recent studies have demonstrated that AgRP neurones are involved in metabolic and behavioural adaptation to an energy deficit to improve survival. In the present study, we used a neuronal subtype-specific GHS-R knockout mouse (AgRP-Cre;Ghsrf/f ) to investigate the role of GHS-R in hypothalamic AgRP neurones in metabolic and behavioural adaptation to hypocaloric restricted feeding. We subjected the mice to a restricted feeding regimen of 40% mild calorie restriction (CR), with one-quarter of food allotment given in the beginning of the light cycle and three-quarters given at the beginning of the dark cycle, to mimic normal mouse intake pattern. The CR-fed AgRP-Cre;Ghsrf/f mice exhibited reductions in body weight, fat mass and blood glucose. Metabolic profiling of these CR-fed AgRP-Cre;Ghsrf/f mice showed a trend toward reduced basal metabolic rate, significantly reduced core body temperature and a decreased expression of thermogenic genes in brown adipose tissue. This suggests a metabolic reset to a lower threshold. Significantly increased physical activity, a trend toward increased food anticipatory behaviour and altered fuel preferences were also observed in these mice. In addition, these CR-fed AgRP-Cre;Ghsrf/f mice exhibited a decreased counter-regulatory response, showing impaired hepatic glucose production. Lastly, hypothalamic gene expression in AgRP-Cre;Ghsrf/f mice revealed increased AgRP expression and a decreased expression of genes in ?-oxidation pathways. In summary, our data suggest that GHS-R in AgRP neurones is a key component of the neurocircuitry involved in metabolic adaptation to calorie restriction.

Dataset Information

The GOAT-ghrelin system is not essential for hypoglycemia prevention during prolonged calorie restriction.

Objective

Methodology

Principal findings

Conclusion

Publications

The GOAT-ghrelin system is not essential for hypoglycemia prevention during prolonged calorie restriction.

Similar Datasets

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